fig08: Myostatin has no direct effect on vasculature. A through D, Myostatin incubation has no effect on vasodilation in mesenteric arteries of all genotypes. Concentration‐response curves to acetylcholine were performed in mesenteric arteries from lean, lean myostatin−/−, db/db, and db/db myostatin−/− mice in the absence (■) or in the presence (◊) of myostatin (20 ng/mL for 30 minutes). E, Myostatin mRNA expression in mesenteric artery of all 4 genotypes. F, AcvRIIB mRNA expression in mesenteric artery of all 4 genotypes. Data are shown as mean±SEM (A through D: n=3 to 8; E and F: n=6). db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes.

Mentions:
All data are reported as means±SEM, with “n” representing the number of mice used in each of the experimental groups. Concentration‐response curves from isolated mesenteric arteries (Figures 7 and 8) were computer fitted to a sigmoidal curve using nonlinear regression (Prism version 5.0; GraphPad Software Inc., San Diego, CA). Maximum vessel relaxation to agonists (Figures 7D, 10A, 11D, and 12A) was measured as a percentage of preconstriction to PE and was analyzed using a multivariable regression analysis in NCSS software (NCSS, LLC, Kaysville, UT). Figure 1A was analyzed using a 1‐way ANOVA and Tukey's multiple comparisons to test myostatin mRNA level difference among different tissues. In Figure 8A through 8D, results were ranked and a 2‐way ANOVA was performed on the ranks. There were 3‐full‐model repeated‐measures analyses. All 3 used the same 2 between factors, which were factor 1 (lean versus obese) and factor 2 (with versus without myostation). For GTT results (Figure 6), the within factor was time. For vessel response curves (Figure 7), the one within factor was different doses ranging from 10−9 to 10−4 mol/L. For the passive mechanical measurements (Figure 13), within factor was pressure. All 3 full‐model repeated‐measures ANOVA were performed using the NCSS software. All remaining experiments were analyzed using a 2‐way ANOVA with Bonferroni's multiple comparisons test. The 2 factors in the 2‐way ANOVA was factor 1 (lean versus obese) and factor 2 (with versus without myostation). Figure 8A through 8D was analyzed using nonparametric repeated measurement. For all analyses, statistical significance was accepted at P<0.05.

fig08: Myostatin has no direct effect on vasculature. A through D, Myostatin incubation has no effect on vasodilation in mesenteric arteries of all genotypes. Concentration‐response curves to acetylcholine were performed in mesenteric arteries from lean, lean myostatin−/−, db/db, and db/db myostatin−/− mice in the absence (■) or in the presence (◊) of myostatin (20 ng/mL for 30 minutes). E, Myostatin mRNA expression in mesenteric artery of all 4 genotypes. F, AcvRIIB mRNA expression in mesenteric artery of all 4 genotypes. Data are shown as mean±SEM (A through D: n=3 to 8; E and F: n=6). db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes.

Mentions:
All data are reported as means±SEM, with “n” representing the number of mice used in each of the experimental groups. Concentration‐response curves from isolated mesenteric arteries (Figures 7 and 8) were computer fitted to a sigmoidal curve using nonlinear regression (Prism version 5.0; GraphPad Software Inc., San Diego, CA). Maximum vessel relaxation to agonists (Figures 7D, 10A, 11D, and 12A) was measured as a percentage of preconstriction to PE and was analyzed using a multivariable regression analysis in NCSS software (NCSS, LLC, Kaysville, UT). Figure 1A was analyzed using a 1‐way ANOVA and Tukey's multiple comparisons to test myostatin mRNA level difference among different tissues. In Figure 8A through 8D, results were ranked and a 2‐way ANOVA was performed on the ranks. There were 3‐full‐model repeated‐measures analyses. All 3 used the same 2 between factors, which were factor 1 (lean versus obese) and factor 2 (with versus without myostation). For GTT results (Figure 6), the within factor was time. For vessel response curves (Figure 7), the one within factor was different doses ranging from 10−9 to 10−4 mol/L. For the passive mechanical measurements (Figure 13), within factor was pressure. All 3 full‐model repeated‐measures ANOVA were performed using the NCSS software. All remaining experiments were analyzed using a 2‐way ANOVA with Bonferroni's multiple comparisons test. The 2 factors in the 2‐way ANOVA was factor 1 (lean versus obese) and factor 2 (with versus without myostation). Figure 8A through 8D was analyzed using nonparametric repeated measurement. For all analyses, statistical significance was accepted at P<0.05.

Bottom Line:
Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training.This impairment was improved by superoxide dismutase mimic Tempol.This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME).